The present invention is directed to sample handling. More particularly, certain embodiments of the present invention provide sample containers adapted for acoustic ejections and analyses and methods thereof as well as compatibility with identification of the container. Merely by way of example, the invention has been applied to a biological sample container with an identification mark, such as a barcode, that is embedded within the container, that identifies the container, and that can be viewed from many different points around the container, with each viewing resulting in identification of the container. But it would be recognized that the invention has a much broader range of applicability, such as storing a fluid sample, or any other item or material, within an identifiable container.
It is often desired to take a chemical or biological sample (e.g., a human blood sample) contained in an individual container and to transfer it to one or more well plates or other objects appropriate for carrying out reactions and assays such as in high-throughput screening for drug discovery or in clinical diagnostics in automated clinical chemistry analyzers. An important feature for the handling of samples includes the ability to transfer small volumes from the container to enable various types of diagnostics that can benefit from consistent deliveries of small-volume samples and to be able to repeatedly extract sample from the same container without potential for confusion of the identity of the sample container.
Acoustic ejection has been known for a number of years as a way of performing transfers of samples from containers, including microplates and microtubes. For example, in a typical setup for acoustic ejection, a piezoelectric transducer is driven by a waveform chosen by a controller and in response generates acoustic energy. The acoustic energy often is focused by an acoustic lens, and coupled to a reservoir or container containing fluid through an acoustic coupling medium (e.g., water). If the focused energy has a focal point inside a fluid in the container and close to a free surface of that fluid, a droplet may be ejected. Droplet size and velocity can be controlled by the chosen waveform as mentioned above.
In some embodiments, the transducer is movable in one or more directions (e.g., in the “z direction”) that is roughly perpendicular to the free surface of the fluid. The movement can take place under the control of the controller. Some acoustic instruments for high-throughput use rely on an active control of the transducer position relative to the container and address the multiplicity of reservoirs in microplates or to an individual tube or to a tube in a rack of tubes. Often, the adjustment of the transducer position involves sending a motion command to a motion controller which then initiates movement in one or more directions (e.g., along one or more axes). For example, motion in the horizontal plane (e.g., in the “x direction” and/or in the “y direction”) aligns the transducer with the selected reservoir, and motion in the vertical direction (e.g., in the “z direction”) is used both to audit the reservoir and to focus for droplet transfer. In another example, positioning of the transducer to achieve the proper focus for droplet ejections can be responsive to data collected from an acoustic audit. Additionally, U.S. Pat. Nos. 6,938,995 and 7,900,505 are incorporated by reference herein for all purposes. When the motion is complete, the controller can notify the system that the transducer and the selected reservoir are now in the proper position for the next step in the process. This may be further measurement of the fluid in the reservoir and/or acoustic ejection of droplets. When completed, the first reservoir is removed, and the acoustic coupling with a second reservoir may take place. Coupling fluid may remain attached to the first reservoir and would typically be at the surface facing the transducer.
Containers may include one or more fluid reservoirs. For example, a container may include one reservoir such as individual tubes, or may include a rack of separable tubes, or may include a microplate having non-separable wells. Paper-based, adhesive labels having barcodes printed thereon are a common identifier for each of these containers and are well known in the art for both tube and microplate identification. Typically, for larger tubes, the barcode label is affixed to the outer surface of the cylindrical wall or to the bottom of the tube, whereas smaller tubes may not be labeled, but instead may be placed into a known location within a microplate or rack having a barcode label affixed thereto, e.g., applied to one or more of the exterior side surfaces. RFID tags have also been used, yet are not as common. In some cases, this is due to cost of tags and readers, and amongst others, it is the requirement to isolate a single item being read from its close neighbors.
As is known in the art, the specific region of the object having the barcode label affixed thereto must be presented to a barcode reader for proper identification to take place. However, problems may arise if the carrier, a label, another object, or the orientation of the object occludes the reader from viewing all or a portion of the complete barcode label, marking, or other identifier.